INTERLEUKIN-8 INDUCES PROLIFERATION OF ENDOMETRIAL STROMAL CELLS - A POTENTIAL AUTOCRINE GROWTH-FACTOR

Proliferation of endometrium is dependent on sex steroid hormones, but specific growth factors are likely to play an important role in regul ating this process. A number of cytokines and growth factors are synth esized in the endometrium in response to sex steroid hormones and act to regulate endometrial function. Endometrial cells produce interleuki n-8 (IL-8) both in vivo and in vitro. We hypothesized that IL-8, a neu trophil chemoattractant/activating factor and a potent angiogenic agen t that has been shown to stimulate growth in other cell types, may dir ectly stimulate proliferation of endometrial cells. We first investiga ted the effect of IL-8 and mouse antihuman-IL-8 neutralizing antibody on endometrial stromal cell proliferation using both a colorimetric as say and thymidine uptake. We then investigated the modulation of endom etrial stromal cell IL-8 production and proliferation by antisense oli gonucleotides specific for IL-8. There was a concentration-dependent i ncrease of cell proliferation with IL-8 (2-fold at 1 ng/mL; P < 0.01 b etween control and concentrations above 0.01 ng/mL) and a concentratio n-dependent inhibition of cell proliferation with anti-IL-8 antibody ( to 30% of the control at 1 mu g/mL; P < 0.01 between control and conce ntrations above 0.1 mu g/mL). IL-8 antisense oligonucleotide treatment decreased IL-8 production by endometrial stromal cells in culture as well as cell proliferation when it is compared with scrambled (nonsens e) oligonucleotide treatment (P < 0.01). Addition of IL-8 (1 ng/mL) re versed the proliferation inhibitory effect of IL-8 antisense oligonucl eotides. We propose that IL-8 may act as an autocrine growth factor in the endometrium, and suggest that it may also play a role in the path ogenesis of endometriosis.